Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines.

Ertan Küçüksayan,Tomris Ozben,Carla Ferreri,Chryssostomos Chatgilialoglu,Demet Tekeli,Günel Talibova,Anna Sansone

doi:10.3390/cells11020225

Abstract

The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell lines of the same cancer type. We used 50 μM sapienic acid supplementation, a non-toxic concentration, to cultivate MCF-7 and 2 triple-negative breast cancer cells (TNBC), MDA-MB-231 and BT-20. We followed up for three hours regarding membrane fatty acid remodeling by fatty acid-based membrane lipidome analysis and expression/phosphorylation of EGFR (epithelial growth factor receptor), mTOR (mammalian target of rapamycin) and AKT (protein kinase B) by Western blotting as an oncogenic signaling cascade. Results evidenced consistent differences among the three cell lines in the metabolism of n-10 fatty acids and signaling. Here, a new scenario is proposed for the role of sapienic acid: one based on changes in membrane composition and properties, and the other based on changes in expression/activation of growth factors and signaling cascades. This knowledge can indicate additional players and synergies in breast cancer cell metabolism, inspiring translational applications of tailored membrane lipid strategies to assist pharmacological interventions.

Highlights

Cancer metabolism and invasiveness rely on monounsaturated and polyunsaturated fatty acids (MUFA and PUFA), which play structural and functional roles, as hydrophobic residues of membrane phospholipids and sustaining signaling cascades [1,2,3]
The importance of fatty acids in the cancer cell membrane lipidome has been reported in recent papers and reviews, highlighting the metabolic pathways shown in Scheme 1 [3,4,5,6], i.e., the formation of the monounsaturated fatty acid (MUFA) oleic acid from the saturated fatty acids (SFA) palmitic and stearic acids
Pursuing our interest in n-10 fatty acids, here we present the results of SA supplementation in breast cancer cells, studied in terms of membrane FA incorporation and remodeling, and associating for the first time the oncogenic signaling cascade of EGFR, AKT and mTOR [21]

Summary

Introduction

Cancer metabolism and invasiveness rely on monounsaturated and polyunsaturated fatty acids (MUFA and PUFA), which play structural and functional roles, as hydrophobic residues of membrane phospholipids and sustaining signaling cascades [1,2,3]. The importance of fatty acids in the cancer cell membrane lipidome has been reported in recent papers and reviews, highlighting the metabolic pathways shown in Scheme 1 [3,4,5,6], i.e., the formation of the MUFA oleic acid from the saturated fatty acids (SFA) palmitic and stearic acids. The desaturase enzyme known as stearoyl-CoA desaturase (SCD-1), carrying out the transformation of stearic acid to oleic acid (Scheme 1), is crucial for cancer development and invasiveness [14,15]. This finding led to specific desaturase inhibition strategies to cause detrimental effects in cancer cell proliferation [16]

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